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Biomedical subjects

N G Levinsky

Publications and source records attributed to N G Levinsky.

At least 55 records · Page 3Linked to original sources
PubMed1981

Prostaglandins mediate the vasodilatory effect of mannitol in the hypoperfused rat kidney.

We have previously reported that mannitol strikingly increases blood flow to rat kidneys hypoperfused at 35-40mm Hg. This vasodilator effect is not due to volume expansion or alterations in plasma osmolality. We have tested the hypothesis that the vasodilatory effect of mannitol in the ischemic rat kidney is mediated by one of the vasoactive renal hormone systems: renin-angiotension, kallikrein-kinin, or prostaglandins. Rats were infused with 5% mannitol in 0.9% saline to 3-5% of body weight. In agreement with our previous studies, RBF increased 1.3 +/- 0.1 ml/min despite maintenance of perfusion pressure at 35-40 mm Hg. The cyclooxygenase inhibitors, meclofenamate and indomethacin had no effect on renal blood flow (RBF) in hypoperfused kidneys. However, in rats pretreated with these inhibitors, expansion with mannitol increased RBF by only 0.37 +/- 0.02 ml/min, 28% of the response in the untreated group (p less than 0.001). Infusion of prostacyclin (PGI2) into the renal artery during reduced perfusion resulted in an increase in RBF of 1.0 +/- 0.1 ml/min. Subsequent expansion with mannitol increased RBF by only 0.5 +/- 0.1 ml/min more, less than one-half of the effect of mannitol in a concurrent group of rats not treated with PGI2. Unlike PGI2 prostaglandin E2 had only a minimal vasodilator effect during hyperperfusion. Imidazole, an inhibitor of thromboxane synthesis, did not alter RBF or renal vascular resistance during hypoperfusion. Treatment of rats during hypoperfusion. with the angiotensin-converting enzyme (kininase II) inhibitor teprotide increased RBF by 1.1 +/- 0.3 ml/min. However, teprotide did not alter the vascular response to mannitol: RBF increased 1.2 +/- 0.1 ml/min more when mannitol was infused into teprotide-treated rats. The renal vascular response to mannitol was not altered by treatment with aprotinin, an inhibitor of the kallikrein-kinin system. Aprotinin was ineffective whether given before or after the vascular response to mannitol was established. We conclude that the vasodilator response to mannitol in the ischemic rat kidney is mediated in large part by increased prostaglandin (PGI2) activity. The failure of converting enzyme inhibition and aprotinin to block the vasodilator response to mannitol is evidence against a role for the renin-angiotension or kallikreinkinin systems in mediating the vasodilator response.

Animals↗
PubMed1979

Choline uptake into renal phospholipids following renal ischemia in rats.

Renal phospholipid metabolism was studied after ischemia was induced by occlusion of the left renal artery in the rat. There was no change in the rate of cellular [14C]choline uptake after 25 or 60 minutes of ischemia. However, [14C]choline incorporation into phospholipid was two to three times greater in slices from the ischemic kidney than in slices from the contralateral control kidney. The increase occurred after 25 minutes of ischemia plus 15 minutes of reflow, and after 60 minutes of ischemia with or without reflow. When [14C]choline was injected into rats after a 60-minute period of renal ischemia, the rate of incorporation into phospholipid in the ischemic kidney was almost twice that of the control kidney. These results were similar to those of the in vitro experiments. Since virtually all of the cellular phospholipids of the kidney are present in cellular membranes, renal ischemia affects membrane metabolism. The mean distribution ratio of alpha-aminoisobutyric acid in slices of kidneys ischemic for 60 minutes was similar to that of control slices: 4.11 +/- 0.2 (SEM) vs. 4.30 +/- 0.30. The normal uptake of alpha-aminoisobutyric acid indicates that the increased incorporation of choline is associated with functional integrity of the membrane.

Aminoisobutyric Acids↗
PubMed1979

Effect of volume expansion on hemodynamics of the hypoperfused rat kidney.

The hemodynamics of the rat kidney were studied during reduction of renal arterial pressure to 35-40 mm Hg (H), and after volume expansion at that pressure with 0.9% NaCl (IS), 1.7% NaCl (HS), 5% mannitol in 0.9% NaCl (MS), 5% mannitol in water (MW), or 50 mM mannitol + 125 mM NaCl. During H, left renal blood flow (RBF) was 0.8+/-0.1 ml/min. Expansion with IS did not alter RBF, but expansion with HS, MS, MW, and 50 + 125 mM NaCl elevated RBF to 200-250% of hypoperfusion values. Glomerular capillary pressure rose significantly from 15.7+/-0.7 mm Hg during H to 22.3+/-1.1, 24.4+/-0.7, and 26.6+/-0.7 mm Hg following expansion with HS, MS, or MW, respectively. Efferent arteriolar pressure also rose significantly to 6.9+/-0.5, 9.7+/-0.8, and 9.5+/-0.9 mm Hg, respectively. Preglomerular resistance fell to 18-24% of H values, and postglomerular resistance fell to 58-74% of H values after expansion with HS, MS, or MW. Glomerular filtration (GFR) could not be detected during H or after IS expansion. HS and mannitol-containing solutions restored GFR to 0.10+/-0.02-0.15+/-0.02 ml/min, and single nephron glomerular filtration to 6-12 nl/min. Papaverine, acetylcholine, and kinins had no effect on RBF or GFR at a perfusion pressure of 35-40 mm Hg. We conclude that mannitol and HS have the capacity to augment RBF during hypoperfusion by reducing arteriolar resistance. The mechanism of the rise in RBF is uncertain; it may be due to changes in effective osmolality of the extracellular fluid or to a direct action of mannitol on vascular smooth muscle. Other potent vasodilators were ineffective during hypoperfusion. Restoration of GFR occurs as a result of the combined effects of augmented RBF and elevated net filtration pressure.

Animals↗
PubMed1978

Renal sodium retention during volume expansion in experimental nephrotic syndrome.

We have studied sodium retention during volume expansion in rats with autologous immune complex nephropathy (AICN), a model of nephrotic syndrome (NS) in which GFR after volume expansion was not different from that in adjuvant-injected controls (C). AICN rats developed heavy proteinuria (298 +/- 27 vs. less than 10 mg/day), hypoalbuminemia (2.14 +/- 0.15 vs. 3.08 +/- 0.12 g/100 ml) and hypercholesterolemia (181 +/- 22 vs. 58 +/- 4 mg/100 ml). After saline, there were no significant differences in blood pressure (119 +/- 2 vs. 114 +/- 2 mm Hg), renal plasma flow (4.9 +/- 0.41 vs. 4.1 +/- 0.28 ml/min), inulin clearance (1.37 +/- 0.06 vs. 1.55 +/- 0.10 ml/min), or SNGFR (47 +/- 2 vs. 53 +/- 4 nl/min). Sodium excretion, however, was significantly lower in NS rats (4.7 +/- 1.1 vs. 9.2 +/- 1.2 muEq/min). Proximal sodium reabsorption was decreased in NS rats (35 +/- 2 vs. 41 +/- 2%, 2.5 +/- 0.2 vs. 3.3 +/- 0.2 nEq/min). Sodium delivery into the loop, however, was equal in NS and C, since the slightly lower filtered load in NS rats offset the depression in proximal reabsorption. Sodium reabsorption by the loop and by the distal convoluted tubules were equal in NS and C. Thus, sodium delivered into the cortical collecting ducts was the same in both groups (0.33 +/- 0.17 vs. 0.34 +/- 0.07 nEq/min; 4.5 +/- 0.6% of filtered sodium vs. 4.4 +/- 0.3%). The percent of filtered sodium excreted in the urine, however, was significantly lower in the NS rats, 2.18 +/- 0.48% vs. 4.0 +/- 0.58%. We conclude that antinatriuresis in this model of NS is determined beyond the superficial late distal convoluted tubule. The inability to excrete the sodium load during volume expansion is due to either enhanced reabsorption by the collecting duct or to abnormal function in deep nephrons.

Animals↗
PubMed1978

Ischemic damage and repair in the rat proximal tubule: differences among the S1, S2, and S3 segments.

Rats were subjected to 25 min of unilateral renal artery occlusion and were studied at 5, 15, and 30 min and at 1, 2, 4, 8, 16, 24, and 48 hr following ischemia. The patterns of epithelial injury and repair in proximal tubule (PT) segments S1, S2, and S3 were followed, and associated changes in renal function were determined. We found that S1 and S2 cells alike are only reversibly injured and recover completely to normalcy within 4 hr, whereas S3 cells selectively undergo progressive cell injury and death and are exfoliated into tubular lumina. The necrotic S3 cells are replaced by mitotic division of survivor cells 24 to 48 hr following the ischemic insult. In addition, there was selective damage within tubular cells. Wiithin 5 min of blood reflow following ischemia, the majority of brush border microvilli (MV) in all three PT segments underwent coalescence by membrane fusion and thus were interiorized into the cytoplasm of PT cells. A minority of MV fragmented and were shed into PT lumina, but nephron obstruction by shed membranes was only mild and transient, unlike in the 1-hr ischemia model. Loss of MV reached a maximum of 15 min. By 30 min, MV began to reappear; by 2 hr, large numbers of MV had been regenerated; and by 4 hr, S1 and S2 cells appeared normal. The regenerative process included the luminal repositioning of previously interiorized MV membrane. MV regeneration occurred in S3 segments also, but before the process was complete, the cells developed features of irreversible cellular injury. Glomerular filtration rate (GFR) was 22% of control at 30 min of reflow, rose progressively to 55% of normal by 7 to 8 hr, and was normal at 24 hr. Single nephron filtration rate (SNGFR) was not significantly different from normal throughout. Proximal tubular sodium reabsorption was depressed and urinary sodium excretion increased at 30 min and at 2 to 3 hr, i.e., at times when MV alterations were prominent, but both were normal by 7 to 8 hr when MV in S1 and S2 cells had been fully reconstituted. Our major conclusions are: 1) There is differential susceptibility by cell type to ischemic injury in rat PT. 2) A rapid brush border loss/regeneration cycle occurs after ischemic injury. 3) Intact brush border may be required for normal sodium reabsorption by PT. Reasons for the GFR/SNGFR discrepancy are unclear, but tubular malfunction may partly explain the phenomenon.

Animals↗
PubMed1977

Collateral circulation after renal artery occlusion in the rat.

We used angiographic and microsphere methods to evaluate the anatomic and functional features of renal collateral circulation in the rat. By the microsphere method, renal parenchymal blood flow was less than 1% of control 1 hour after occlusion of the main renal artery; 2.8% of control 1-2 weeks after arterial occlusion; and 1% of control 4-9 weeks after occlusion. Radiographic observations during chronic occlusion revealed numerous collateral vessels to the kidney. These vessels readily filled with angiographic contrast medium but the intrarenal circulation did not visualize. We conclude that collateral circulation to renal parenchyma is negligible after acute or chronic occlusion of the main renal artery in the rat. The rich anatomic plexus of collateral vessels has no functional significance and is unable to preserve viability of the parenchyma.

Acute Disease↗
PubMed1977

Evidence that decreased cardiac output is not the stimulus to sodium retention during acute constriction of the vena cava.

It has been proposed that the antinatriuresis during constriction of the TVC is due to a decrease in CO. We have compared the effect on sodium excretion of comparable reductions in CO by three separate methods: TVC constriction, PA occlusion, and LV infarction. Dogs were studied during 10% of body weight saline loading and again after TVC constriction, PA occlusion, or LV infarction. CO fell 26 to 31% in all groups; sodium excretion was not significantly altered after PA occlusion (474 to 533 micronEq/min.) or LV infarction (587 to 609 micronEq/min.) but fell significantly after TVC constriction (504 to 271 micronEq/min.). Renal and systemic hemodynamoderate reduction of CO per se does not cause sodium retention. PA and TVC dogs had comparable increments in vena caval pressure but opposite changes in RVEDP; 4 to 0.9 mm. Hg (TVC) and 0.5 to 9.1 mm. Hg (PA).

Animals↗
PubMed1975

The effect of ischemia on renal blood flow in the dog.

Renal blood flow (RBF) and the distribution of cortical blood flow (microspheres) were measured in the dog after 90 min of total unilateral renal ischemia. RBF was 21% greater than control 2 min after release of the renal artery occlusion, and returned toward control 60 min later. At 2 min after release there was a small but significant increment in deep cortical blood flow which reverted to control by 60 min. When renal artery occlusion was maintained for 180 min, return of blood flow was blunted at 2 min after release of the occlusion, but was not significantly different from control within 10 min after release. Clearance rates of inulin and para-aminohippurate (Cin and Cpah) were 81 and 82% below control after release of occlusion. These data demonstrate that in the dog there is prompt and complete return of blood flow to or above control levels after complete renal artery occlusion. There was no evidence for the "no-reflow" phenomenon.

Aminohippuric Acids↗
PubMed1975

Effect of hemodilution on the distribution of renal blood flow.

We evaluated the effects of hemodilution, expansion of intravascular volume, and expansion of interstitial volume on the distribution of cortical renal blood flow, utilizing the microsphere technique. Hemodilution without volume expansion (saline exchange) produced an increase in fractional blood flow in zone 1 (outermost zone) of the cortex from 34 plus or minus 1% to 43 plus or minus 2% and a decrease in fractional blood flow in zone 4 (innermost zone) from 16 plus or minus 2% to 13 plus or minus 2%. Hemodilution without volume expansion or a decrease in plasma protein concentration (isoncotic exchange) produced a similar redistribution in blood flow in zone 1 from 34 plus or minus 2% to 41 plus or minus 2% and in zone 4 from 14 plus or minus 2% to 10 plus or minus 1%. Hemodilution with intravascular volume expansion (hyperoncotic albumin infusion) also produced a superficial shift; blood flow in zone 1 increased from 27 plus or minus 1% to 30 plus or minus 1% and that in zone 4 decreased from 19 plus or minus 2% to 15 plus or minus 1%. Previous studies have demonstrated a redistribution to the juxtamedullary area after saline expansion. Our data demonstrate that hemodilution causes flow to redistribute to the superficial rather than the deep cortex. This superficial shift appears to be secondary to decrease hematocrit rather than to dilution of plasma proteins or expansions of intravascular volume. The deep shift in cortical blood flow which occurs during saline loading is presumably a consequence of expansion of interstitial volume.

Animals↗
PubMed1974

Natriuretic hormones.

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Adenosine Triphosphatases↗